Disazo compounds for therapeutic use



Patented Nov. 6, 1934 UNITED STATE PATENT oer-Ice 1,979,678 DI SAZQCOMPOUNIIIJLTSSE OR THERAPEUTIC Joseph Ebert, Westmont, N. J., assignorto The Farastan Company, Philadelphia, Pa., a corporation ofPennsylvania No Drawing. Application October 15, 1931, Serial No.569,120

Claims.

amine or an aromatic carboxylic acid or carboxylate. The carboxylic acidor carboxylate may be an amino derivative or an hydroxy derivative; itmay be an amino-'hydroxy derivative ,or other modified derivative: suchas a methyl-- hydroxy derivative. The amine may be an aromatic diamineor an alkoxy aromatic amine.

The nucleus of the diamino compound from which the disazo compounds ofthis invention are prepared may be a phenyl residue, a diphenyl residue,or a diphenyl methane residue, hereinafter referred to in the claims asresidues of the benzene series. The residue may contain an alkyl group,for example N=NC6IIs-CHs--N=N- or an alkoxy group, for exampleN=N--CsI-ls- OC2H5--CH2C6H3OC2H5N=N. The disazo compounds of thisinvention are non-toxic. They contain no nitro, sulfonic, chlorine,bromine, or iodine groups.

The disazo compounds of this invention possess pronounced bactericidaland bacteriostatic value and have a distinct analgesic action. Thebactericidal value is at least 1 to 1500 and the bacteriostatic value isat least 1 to 60,000. The color of the compounds ranges from a brownishred to a dark red. Their alkali metal salts are practically insolubleinwater; their hydrochlorides and sulfates are more soluble in water. Thelow toxicity of these compounds, their colloidal character and theircolor make them particularly advantageous for use in the treatment ofintestinal and genito-urinary disorders. The compounds may be used inthe form of their alkali metal salts, their hydrochlorides, theirsulfates, or the free bases, all of which are solublein the commonorganic solvents such as alcohols and acetone. i 5

.The;following examples illustrate the invention but it-is intended andis to be understood that the invention is not limited to the specificexamples given below. In connection with EX- 0 ample l the method ofpreparation is given somewhat in detail. The other examples may beprepared by tetrazotizing one molecular weight of a diamino nucleus andcoupling this with two molecular. weights of ortho-hydroxy-quinoline or5 one molecular weight of ortho-hydroxy-quinoline and one molecularweight of a proper carboxylic acid or aromatic amine. The compounds thusobtained as salts may be purified and the hydrochlorides or sulfates orthe free bases may be formed from the salts in the manner well-known inthe art.

EXAMPLE 1 Sodium salt of diphenyl-disazo-o-hydromy- {Iquinoline-o-amino-benzoic acid of o-amino-benzoic acid in .12 parts ofconcentrated hydrochloric acid and 100 parts of water. The coupling iscarried out at a temperature of 15 to 25 C. The mixture is then madealkaline by the additionof a 10 to 20% solution of sodium hydroxide. Thesodium salt separates out as a reddish-brown precipitate. Thisprecipitate is filtered out and washed with water until free fromchloride and then dried. The sodium salt may be purified byrecrystallizing it from alcohol.

EXAMPLE 2 Sodium salt of diphenyl-disazo-o-hydroacy-quino-Zine-o-hydroxy-benzoic acid Prepared from benzidine, o-hydroxy-quinolineand salicylic acid.

EXAMPLE 3 Sodium salt of toluene-disazo-o-hydrozcy-quino- 105Zine-5-amino-hydroxy-benzoic acid CnH0ONN=N(3)G H OH (4)(1)N=NCtHz-OH(1)oooNao Prepared from m-toluylenediamine, o-hydroxyquinoline and5-amino-hydroXy-benzoic acid.

Prepared from benzidine, m-phenylene-diamine and o-hydroxy-quinoline.

EXAMPLE 5- Diphenyl disazo-o-amino-ethomy phenol -o-hydroxy-quinolz'neOCQHHZ).

O HnONN=NCaH4CH N=NC H| I Prepared from benzidine, o-phenetidine andohydroxy-quinolinef EXAMPLE 6 DitoZyZ-disazo-o-amino-metho.ry phenol 0hydromyquinoline EXAMPLE 11 Sodium salt ofbenzene-disazo-o-hydroxy-quino- Zine-o-hydromy benzoic acid 011(1CnHflON-N=N(1)CH (3)N=NG H5 Prepared from m-phenylene diarnine,o-hydroXyquinoline and o-hydroxy benzoic acid.

EXAMPLE 12 Benzene disaeo 0 amino ethomy phenol o hydrory-quinolineO,HuONN=N(1)O H4(3)N=NC:H:

NHzO) Prepared from m-phenylene diamine, o-phenetidine and o-hydroxyquinoline.

EXAMPLE 13 quinoline Prepared from o-tolidine, o-anisidine and o-hy-Prepared from diphenyl methane,

droxy-quinoline.

' EXAMPLE '7 Benzene-disdzo-m-phenylene diamine-o-hydroscy-quinoline andohydroXy-quino1ine (2 mol.).

EXAMPLE 14 Sodium salt of diphenyl methane-diethowydisaeo-o-hydro:cy-quinoline-o-amino benzoic acid NHIQ) I i V I NHzu) C,,0 =N 1 -o oam-mmwm-dm-oOQH5(2)(1)N=N JGH:

o 0 0 Na (2 Prepared from m pheny'lene diainine, n l-phenylene diamineand o-hydroxy-quinoline.

Sodium salt of benzene-disazo-o hydroxy-quinm Zine-o-amino benzoic acidNH2(1) onHuoN-N='N(1 --ou1.- s N=N ouH3 o 0 ONa(2) Prepared fromm-phenylenediamine, o-hydroxyquinoline and o-amino benzoic acid.

Prepared from diamino-diethoXy-dipheny1 methane-o-hydroxy-quinoline ando-amino benzoic acid.

EXAMPLE 15 Sodium salt of diphenyZ-disazo-o-hydroxy-quinc-Zine-p-hydromymetatoluic acid C HQONN=N0aH4-GiH4N=NOeH -OH;(5)

i o 0 ONa(1) Prepared from benzidine, 'o-hydroxy-quinoline andp-cresotic acid.

In the claims, the group CQHBON indicates an hydroxy quinoline radicalin which the nitrogen and OH groups are in different rings as in aderivative of o-hydroxy-duinoline.

I claim:

1. A non-toxic disazo compound having the general formulaR--N=N-R-N=N--C9H6ON where --N=NRN=N is a disazotizednucleus of thebenzene series and R is ohydroxyquinoline, an aromatic diamine of thebenzene series, an alkoxy aromatic amine of the benzene series, an aminocarboxylic acid or carboxylate of the benzene series, or an hydroXycarboxylic acid or carboxylate of the benzene series.

2. A non-toxic disazo compound having the general formulaR'N=NR-N=N-C9I-I6ON zene series, or an hydroxy carboxylic acid orcarboxylate of the benzene series and has a bactericidal value of atleast 1 to 1500 and a bacteriostatic value of at least 1 to 60,000.

4. Sodium salt of diphenyl-disazo-o-hydroxw quinoline-o-amino-benzoicacid.

5. Sodium salt oftoluene-disazo-o-hydr0xyquino1ine-5-amino-hydroxy-benzoic acid.

JOSEPH EBERT.

